Renal glucose release during hypoglycemia is partly controlled by sympathetic nerves - a study in pigs with unilateral surgically denervated kidneys.

Sabine J Bischoff,Matthias Schwab,Georg Matziolis,Martin Schmidt,René Schiffner,Thomas Lehmann,Alexander Saemann

doi:10.14814/phy2.12603

Sabine J Bischoff, Matthias Schwab + Show 5 more

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https://doi.org/10.14814/phy2.12603

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Abstract

Catecholamines are known to increase renal glucose release during hypoglycemia. The specific extent of the contribution of different sources of catecholamines, endocrine delivery via circulation or release from autonomous sympathetic renal nerves, though, is unknown. We tested the hypothesis that sympathetic renal innervation plays a major role in the regulation of renal gluconeogenesis. For this purpose, instrumented adolescent pigs had one kidney surgically denervated while the other kidney served as a control. A hypoglycemic clamp with arterial blood glucose below 2 mmol/L was maintained for 75 min. Arteriovenous blood glucose difference, inulin clearance, p-aminohippurate clearance, and sodium excretion were measured in intervals of 15 min separately for both kidneys. Blood glucose was lowered to 0.84 ± 0.33 mmol/L for 75 min. The side-dependent renal net glucose release (SGN) decreased significantly after the unilateral ablation of renal nerves. In the linear mixed model, renal denervation had a significant inhibitory effect on renal net glucose release (P = 0.036). The SGN of the ablated kidney decreased by 0.02 mmol/min and was equivalent to 43.3 ± 23.2% of the control (nonablated) kidney in the pigs. This allows the conclusion that renal glucose release is partly controlled by sympathetic nerves. This may be relevant in humans as well, and could explain the increased risk of severe hypoglycemia of patients with diabetes mellitus and autonomous neuropathy. The effects of denervation on renal glucose metabolism should be critically taken into account when considering renal denervation as a therapy in diabetic patients.

Highlights

The ablation of autonomous nerves, which are attached to the adventitia of renal arteries, is a new interventional method to treat hypertension (Schmieder et al 2012)
The classical indication of renal denervation comprises resistant hypertension, which is frequently associated with metabolic alterations such as overweight and obesity, impaired fasting glucose, and impaired glucose tolerance, as well as insulin resistance
To test our hypothesis that the glucose metabolism is altered by renal denervation we used pigs as an experimental model

Summary

Introduction

The ablation of autonomous nerves, which are attached to the adventitia of renal arteries, is a new interventional method to treat hypertension (Schmieder et al 2012). The classical indication of renal denervation comprises resistant hypertension, which is frequently associated with metabolic alterations such as overweight and obesity, impaired fasting glucose, and impaired glucose tolerance, as well as insulin resistance. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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